A Potential Role for Angiotensin II-Induced Vascular Endothelial Growth Factor Expression in the Pathogenesis of Diabetic Nephropathy?

Diabetic nephropathy often co-exists with other manifestations of microangiopathy, in particular retinopathy. Recent clinical evidence suggests that inhibition of the renin-angiotensin system in humans can delay the development and/or progression of diabetic nephropathy and perhaps also retinopathy. The benefits of this therapeutic strategy may in part be explained by inhibition of the nonhaemodynamic actions of angiotensin II (Ang II). The recognized nonhaemodynamic actions of Ang II include the augmented release of many growth factors. Ang II can stimulate the release of vascular endothelial growth factor (VEGF) from human vascular tissues. VEGF is a family of potent cytokines which act to induce angiogenesis and markedly increase microvascular permeability. VEGF is abundantly expressed in the renal glomerulus, specifically within the podocyte, where its function is unknown. VEGF is also expressed in the retina and increased retinal VEGF expression occurs in diabetes and has been implicated in the pathogenesis of diabetic retinopathy. This review considers the potential clinical significance of Ang II-induced VEGF expression, if any, in the pathogenesis of diabetic nephropathy and retinopathy.

[1]  B. Williams.  Angiotensin II, VEGF, and diabetic retinopathy , 1998, The Lancet.

[2]  H. Hammes,et al.  Upregulation of the vascular endothelial growth factor/vascular endothelial growth factor receptor system in experimental background diabetic retinopathy of the rat. , 1998, Diabetes.

[3]  G. Jerums,et al.  Expression of transforming growth factor-beta1 and type IV collagen in the renal tubulointerstitium in experimental diabetes: effects of ACE inhibition. , 1998, Diabetes.

[4]  A. Sjølie,et al.  Effect of lisinopril on progression of retinopathy in normotensive people with type 1 diabetes , 1998, The Lancet.

[5]  F. Lai,et al.  Gene expression of the renin‐angiotensin system in human kidney , 1998, Journal of hypertension.

[6]  B. Gallacher,et al.  Glucose-Induced Protein Kinase C Activation Regulates Vascular Permeability Factor mRNA Expression and Peptide Production by Human Vascular Smooth Muscle Cells In Vitro , 1997, Diabetes.

[7]  B. Williams,et al.  Factors regulating the expression of vascular permeability/vascular endothelial growth factor by human vascular tissues , 1997, Diabetologia.

[8]  N. Chaturvedi.  Randomised placebo-controlled trial of lisinopril in normotensive patients with insulin-dependent diabetes and normoalbuminuria or microalbuminuria , 1997, The Lancet.

[9]  Y. Hirata,et al.  Molecular cloning of a novel vascular endothelial growth factor, VEGF-D. , 1997, Genomics.

[10]  K. Tomita,et al.  Vascular endothelial growth factor is an essential molecule for mouse kidney development: glomerulogenesis and nephrogenesis. , 1997, The Journal of clinical investigation.

[11]  R. Carey,et al.  Oxygen regulates vascular endothelial growth factor-mediated vasculogenesis and tubulogenesis. , 1997, Developmental biology.

[12]  J. Isner,et al.  Vascular endothelial growth factor/vascular permeability factor augments nitric oxide release from quiescent rabbit and human vascular endothelium. , 1997, Circulation.

[13]  Mayumi Ono,et al.  Induction of Vascular Endothelial Growth Factor by Tumor Necrosis Factor α in Human Glioma Cells , 1996, The Journal of Biological Chemistry.

[14]  B. Williams.  Vascular Permeability/Vascular Endothelial Growth Factors: A Potential Role in the Pathogenesis and Treatment of Vascular Diseases , 1996, Vascular medicine.

[15]  R. Kendall,et al.  Identification of a natural soluble form of the vascular endothelial growth factor receptor, FLT-1, and its heterodimerization with KDR. , 1996, Biochemical and biophysical research communications.

[16]  Lois E. H. Smith,et al.  Oligodeoxynucleotides inhibit retinal neovascularization in a murine model of proliferative retinopathy. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[17]  K. Shulman,et al.  Expression of vascular permeability factor (VPF/VEGF) is altered in many glomerular diseases. , 1996, Journal of the American Society of Nephrology : JASN.

[18]  A. Mantovani,et al.  Migration of human monocytes in response to vascular endothelial growth factor (VEGF) is mediated via the VEGF receptor flt-1. , 1996, Blood.

[19]  K. Alitalo,et al.  Vascular endothelial growth factor B, a novel growth factor for endothelial cells. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[20]  W. Wood,et al.  Vascular endothelial growth factor-related protein: a ligand and specific activator of the tyrosine kinase receptor Flt4. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[21]  L. Aiello,et al.  Suppression of retinal neovascularization in vivo by inhibition of vascular endothelial growth factor (VEGF) using soluble VEGF-receptor chimeric proteins. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[22]  J. McGill,et al.  The beneficial effect of angiotensin-converting enzyme inhibition with captopril on diabetic nephropathy in normotensive IDDM patients with microalbuminuria. North American Microalbuminuria Study Group. , 1995, The American journal of medicine.

[23]  J. Erusalimsky,et al.  Basic fibroblast growth factor upregulates the expression of vascular endothelial growth factor in vascular smooth muscle cells. Synergistic interaction with hypoxia. , 1995, Circulation.

[24]  R. A. Gomez,et al.  Angiotensin II regulates nephrogenesis and renal vascular development. , 1995, The American journal of physiology.

[25]  B. Williams,et al.  Angiotensin II increases vascular permeability factor gene expression by human vascular smooth muscle cells. , 1995, Hypertension.

[26]  B. Williams,et al.  Serum and platelet-derived growth factor-induced expression of vascular permeability factor mRNA by human vascular smooth muscle cells in vitro. , 1995, Clinical science.

[27]  K. Plate,et al.  Expression of vascular endothelial growth factor and its receptors in human renal ontogenesis and in adult kidney. , 1995, The American journal of physiology.

[28]  L. Aiello,et al.  Vascular endothelial growth factor in ocular fluid of patients with diabetic retinopathy and other retinal disorders. , 1994, The New England journal of medicine.

[29]  Atsushi Namiki,et al.  Indirect Angiogenic Cytokines Upregulate VEGF and bFGF Gene Expression in Vascular Smooth Muscle Cells, Whereas Hypoxia Upregulates VEGF Expression Only , 1994 .

[30]  R. Bain,et al.  The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. The Collaborative Study Group. , 1993, The New England journal of medicine.

[31]  R. Bain,et al.  The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. , 1993 .

[32]  D. Connolly,et al.  Human mesangial cells and peripheral blood mononuclear cells produce vascular permeability factor. , 1993, Kidney international.

[33]  B. Kasiske,et al.  Effect of Antihypertensive Therapy on the Kidney in Patients with Diabetes: A Meta-Regression Analysis , 1993, Annals of Internal Medicine.

[34]  E. Keshet,et al.  Vascular endothelial growth factor induced by hypoxia may mediate hypoxia-initiated angiogenesis , 1992, Nature.

[35]  N. Ferrara,et al.  Molecular and biological properties of the vascular endothelial growth factor family of proteins. , 1992, Endocrine reviews.

[36]  R. Blantz,et al.  Effect of angiotensin II on glomerular hemodynamics and ultrafiltration coefficient. , 1987, Kidney international. Supplement.

[37]  B. Brenner,et al.  Prevention of diabetic glomerulopathy by pharmacological amelioration of glomerular capillary hypertension. , 1986, The Journal of clinical investigation.

[38]  K. Alitalo,et al.  A novel vascular endothelial growth factor, VEGF-C, is a ligand for the Flt4 (VEGFR-3) and KDR (VEGFR-2) receptor tyrosine kinases. , 1996, The EMBO journal.

[39]  E. Brogi,et al.  Indirect angiogenic cytokines upregulate VEGF and bFGF gene expression in vascular smooth muscle cells, whereas hypoxia upregulates VEGF expression only. , 1994, Circulation.

[40]  A Fournier,et al.  The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. , 1994, The New England journal of medicine.

[41]  J. Winer,et al.  Binding sites for vascular endothelial growth factor are localized on endothelial cells in adult rat tissues. , 1992, The Journal of clinical investigation.

[42]  P T de Jong,et al.  Renin, prorenin, and immunoreactive renin in vitreous fluid from eyes with and without diabetic retinopathy. , 1989, The Journal of clinical endocrinology and metabolism.

[43]  T. Goodfriend,et al.  Angiotensin Receptors , 1994, Springer US.